The present embodiments relate to devices for detecting fluorescence.
Equipment for fluorescence detection, hereinafter also called fluorescence scanners, can be used to detect various molecular factors. Substances having different molecular properties may have different fluorescent properties, which can be detected in a targeted way. Fluorescence detection is optically based and is noninvasive or minimally invasive. With the knowledge of the applicable fluorescent properties, the molecular nature of a given material being examined may be ascertained.
In medicine, molecular properties, for instance also called a “molecular signature”, provide information about the state of health of a living creature or patient and can be assessed diagnostically. For example, molecular signatures are used for detecting cancer. Still other syndromes, such as rheumatoid arthritis or arteriosclerosis of the carotid artery, can be identified.
For fluorescence detection, the fluorescence is excited, such as by optical excitation. The excitation light is in the infrared range (IR), for instance, or in the near infrared range (NIR). The suitable frequency range is dependent on the substance to be examined. Substances that themselves have no molecular or chemical properties that would be suitable for fluorescence detection can be molecularly “marked” in a suitable way. For instance, markers that with suitable preparation bind to or are deposited only on very special molecules may be used. Such marking may function by a mechanism that in pictorial terms can be thought of as a lock-and-key mechanism. The marker and the molecule to be detected fit one another like a lock and key, while the marker does not bind to other substances. If the marker has known fluorescent properties, then after the binding or deposition, the marker may be optically detected. The detection of the marker allows conclusions to be drawn as to the presence of the marked special substance. For detection, a detector is capable of detecting light in the wavelength that the substance in question, or precisely the marker used, emits upon excitation.
Fluorescence methods examine regions near the surface or in the open body (intraoperative applications). Examples of such investigations are detecting fluorescently marked skin cancer or the detection of tumor boundaries in the resection of fluorescently marked tumors. For example, the company known as NOVADAQ has developed a system for intraoperatively viewing coronary arteries and the function of bypasses (that is, the flow through them).
One subject of research in biotechnology is fluorescent metabolic markers that accumulate only in certain regions, such as tumors, infections, or other foci of disease, or are distributed throughout the body but are activated only in certain regions, for instance by tumor-specific enzyme activities with additional exposure to light.
In medical diagnosis, marker substances, so-called fluorophores, such as indocyanin green (ICG), are known. The marker substances, for example, bind to blood vessels and can be detected optically. In an imaging process, the contrast with which blood vessels are displayed may be enhanced. So-called “smart contrast agents” may be used. These are activatable fluorescence markers that bind, for instance, to tumor tissue and whose fluorescent properties are not activated until the binding to the substance to be marked occurs. Such substances may comprise self-quenched dyes, such as Cy5.5, which are bound to larger molecules by way of specific peptides. The peptides can in turn be detected by specific proteases, produced for instance in tumors, and can be cleaved. The fluorophores are released by the cleavage and are no longer self-quenched, but instead develop fluorescent properties. The released fluorophores can be activated for instance in the near IR wavelength range of around 740 nm. One example of a marker on this basis is AF 750 (Alexa Fluor 750), with a defined absorption and emission spectrum in the wavelength range of 750 nm (excitation) and 780 nm (emission).
In medical diagnosis, such activatable markers may be used, for instance, for intraoperative detection of tumor tissue. The diseased tissue may be identified exactly and then removed. One typical application is the surgical treatment of ovarian cancer. The diseased tissue is typically removed surgically. Because of the increased sensitivity of fluorescence detection, the diseased tissue can be better detected along with various surrounding foci of disease and thus removed more completely.
In the treatment of breast cancer, typical surgical treatments are lumpectomies (or mastectomies) and lymph node sections and lymph node biopsies. Lymph nodes are typically detected optically by means of 99mTc sulfur colloids in combination with low-molecular methylene blue. The radioactive mTc sulfur colloids could be avoided by using fluorescence detection.
In treating these diseases named as examples as well as other syndromes, an operation is typically performed to surgically remove diseased tissue. For aiding in the operation, a fluorescence detection may be performed to improve the detection of the diseased tissue portions to be removed during the ongoing operation or in the open wound. To that end, the tissue parts are marked before the operation with a suitable substance that is then activated by binding to the diseased tissue parts. An apparatus for fluorescence detection should be easy for the surgeon to manipulate and should be usable in the sterile field of the operating room.